Dynamic Phosphorylation of CENP-A at Ser68 Orchestrates Its Cell-Cycle-Dependent Deposition at Centromeres

分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-12

Yu, Zhouliang Zhou, Xiang Wang, Wenjing Deng, Wenqiang Fang, Junnan Hu, Hao Wang, Zichen Cui, Lei Shen, Jing Ou, Guangshuo Yang, Na Chen, Ping Xu, Rui-Ming Li, Guohong Yu, Zhouliang Deng, Wenqiang Fang, Junnan Hu, Hao Peng, Shengyi Li, Shangze

摘要： The H3 histone variant CENP-A is an epigenetic marker critical for the centromere identity and function. However, the precise regulation of the spatiotemporal deposition and propagation of CENP-A at centromeres during the cell cycle is still poorly understood. Here, we show that CENP-A is phosphorylated at Ser68 during early mitosis by Cdk1. Our results demonstrate that phosphorylation of Ser68 eliminates the binding of CENP-A to the assembly factor HJURP, thus preventing the premature loading of CENP-A to the centromere prior to mitotic exit. Because Cdk1 activity is at its minimum at the mitotic exit, the ratio of Cdk1/PP1 alpha activity changes in favor of Ser68 dephosphorylation, thus making CENP-A available for centromeric deposition by HJURP. Thus, we reveal that dynamic phosphorylation of CENP-A Ser68 orchestrates the spatiotemporal assembly of newly synthesized CENP-A at active centromeres during the cell cycle.

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